British journal of clinical pharmacology最新文献

{"title":"Trends in gabapentinoid prescribing: A nationwide Danish drug utilization study.","authors":"Anton Pottegård, Lotte Rasmussen, Morten Olesen, Anne Mette Skov Sørensen, Zandra Nymand Ennis, Joseph Kane, Sarah Baxter, Blánaid Hicks","doi":"10.1002/bcp.70060","DOIUrl":"https://doi.org/10.1002/bcp.70060","url":null,"abstract":"<p><strong>Aims: </strong>Pregabalin and gabapentin are increasingly used for pain and other conditions. Concerns exist about overuse as well as potential misuse and abuse. To guide rational prescribing practices, we provide detailed nationwide data on the use of gabapentinoids in Denmark.</p><p><strong>Methods: </strong>We conducted a nationwide descriptive drug utilization study using the Danish healthcare registries to describe the use of gabapentinoids among Danish adults 2010-2023. We described overall use patterns, temporal trends, user characteristics, skewness of use, treatment duration and concomitant medication use.</p><p><strong>Results: </strong>The prevalence of gabapentinoid use increased almost four-fold from 11 per 1000 adults in 2010 to 41 in 2023 with the highest use among individuals aged 80+ years (96 per 1000 in 2023). Gabapentin and pregabalin were used equally. The median age of users increased from 58 years in 2010 to 63 years in 2023, while a decline was observed in the proportion with concomitant use of other drug classes, including benzodiazepines or opioids. Only 7% of patients were continuously treated for 3 years following initiation, while 22% were currently treated after 3 years (allowing treatment breaks). The use of gabapentinoids were somewhat skewed with 1% of users accounting for 7.3% of use in 2023.</p><p><strong>Conclusion: </strong>The use of gabapentinoids has increased dramatically in recent years, in particular, among the elderly, and adherence was low. Increased attention to the increasing use of gabapentinoids is warranted to ensure rational use of this drug class.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of 4616 clinical trial initial submissions received by the Medicines and Healthcare products Regulatory Agency between February 2019 and October 2023.","authors":"Andrea Manfrin, Kingyin Lee, James Pound, Munir Pirmohamed, June Raine","doi":"10.1002/bcp.70061","DOIUrl":"https://doi.org/10.1002/bcp.70061","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to analyse clinical trial initial submissions received by the MHRA between February 2019 and October 2023.</p><p><strong>Methods: </strong>Data on submissions were extracted from the clinical trials unit data bank. The primary end-point was the type of clinical trial initial submissions. Secondary end-points were sponsor types, participant demographics, healthy volunteers, health categories and studies involving first in human and advanced therapy medicinal products. The analysis used descriptive statistics for all categorical variables.</p><p><strong>Results: </strong>MHRA received 4616 submissions. The highest percentage was in 2020 (22.8%) and the lowest in 2023 (17.2%). Phase 3 submissions were the highest (32.6%) and and phase 4 the lowest (5.2%). Commercial sponsors represented 85.1% of the total submissions. Both sexes were included in most trials (90%), while the number of submissions involving females only (3.7%) was lower than male only trials (6.1%). The elderly population was represented in 67.7% of trials with pregnant and breastfeeding women represented in 1.1% and 0.6% of trials, respectively. Breastfeeding women were not included in phase 1. Paediatric trials mostly involved adolescents. Healthy volunteers were included in 16.5% of the total submissions. The most common health category was cancer (29.4%), with the lowest being pain. First in human submissions represented 12.7% and advanced therapy medicinal products 3.4% of submissions.</p><p><strong>Conclusions: </strong>These results highlight the clinical trial landscape in the United Kingdom and represent an important baseline for policymakers, healthcare providers, sponsors and patients and will enable an assessment of how policy changes can improve the variety and number of clinical trials.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, pharmacodynamics and safety profile of SKB336, a selective inhibitor of coagulation factor XI/XIa in healthy subjects.","authors":"Qian Xiang, Zhiyan Liu, Qiufen Xie, Nan Zhao, Shuang Zhou, Linyu Cao, Xia Zhao, Yaling Li, Jing Si, Qingmei Wu, Junyou Ge, Yimin Cui","doi":"10.1002/bcp.70043","DOIUrl":"https://doi.org/10.1002/bcp.70043","url":null,"abstract":"<p><strong>Aims: </strong>Coagulation factor XI (FXI) plays a crucial role in the intrinsic coagulation pathway, and inhibitors targeting it may mitigate the risk of haemorrhage compared to anticoagulants currently on the market. SKB336, a novel selective inhibitor of FXI/FXIa, has been shown to prolong the activated partial thromboplastin time (APTT) in both in vitro and in vivo studies. This study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of SKB336 in healthy subjects.</p><p><strong>Methods: </strong>In this randomized, single-blinded, placebo-controlled and dose-escalation first-in-human phase I study, 60 healthy subjects were allocated to 6 cohorts (0.1, 0.3, 0.6, 1.25, 2.5 and 4 mg/kg) and received a single subcutaneous injection of SKB336 or placebo in a 4:1 ratio. The safety, tolerability, pharmacokinetics and immunogenicity were measured up to 85 days postdose. Exploratory analysis consisted of FXI activity and APTT.</p><p><strong>Results: </strong>SKB336 was well tolerated in all 6 cohorts, without any haemorrhagic events, reported deaths or serious adverse events. No significant dose-dependent correlation was observed with the incidence of adverse events. Dose-dependent increases in the maximum observed drug concentration and area under the plasma concentration-time curve were observed. The mean elimination half-life was 21.3-33.5 days, indicating a potential monthly dosing frequency. The maximum inhibition rate of FXI activity for all 6 cohorts reached 0, 17, 28, 48, 54 and 59%, respectively. The maximum APTT ratio to baseline reached 1.09-, 1.26-, 1.47-, 1.77, 1.91- and 2.00-fold, respectively.</p><p><strong>Conclusion: </strong>SKB336 was generally tolerated, without any bleeding events in healthy volunteers. Besides, SKB336 presented a persistent dose-dependent prolongation of APTT and duration of FXI inhibition.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The improvement in muscle function following statin withdrawal might involve the repair of the neuromuscular junction.","authors":"Rizwan Qaisar, Asima Karim, Shaea A Alkahtani, Imran Ullah Khan, Firdos Ahmad","doi":"10.1002/bcp.70065","DOIUrl":"https://doi.org/10.1002/bcp.70065","url":null,"abstract":"<p><strong>Aims: </strong>The effects and relative mechanisms of statin usage and withdrawal on subjective and objective muscle functions are poorly known. We investigated the associations of neuromuscular junction (NMJ) degradation to muscle impairment in older adults taking statins.</p><p><strong>Methods: </strong>We recruited male controls (n = 82) and statin users (n = 76) for measuring handgrip strength (HGS), body composition, gait speed, short physical performance battery (SPPB), statin-associated muscle symptoms (SAMS) and plasma c-terminal agrin fragment-22 (CAF22; a marker of NMJ degradation). The statin users were evaluated at baseline, 1 year after statin usage and 6 months after statin withdrawal.</p><p><strong>Results: </strong>One year of statin usage was associated with lower HGS, gait speed, SPPB scores and higher SAMS scores and plasma CAF22 levels (all P < .05). Conversely, 6 months after statin withdrawal, gait speed and SPPB scores were restored with a concurrent reduction in SAMS and CAF22 levels (all P < .05). Correlation analysis revealed significant correlations of plasma CAF22 with HGS, SPPB and SAMS after statin usage and withdrawal (all P < .05). Lastly, statin withdrawal also reduced the plasma creatine kinase levels (P < .05).</p><p><strong>Conclusion: </strong>Altogether, statin usage was associated with muscle and physical decline and an increase in CAF22 and SAMS, which were partly restored after statin withdrawal. Our findings suggest a role for NMJ plasticity in muscle restoration following statin withdrawal.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of early-life and prolonged antibiotics exposure on 78 common diseases: Evidence from epidemiology.","authors":"Yuhan Jiang, Ju Guo, Xueming Yao, Zixuan Wang, Yifan Wang, Ruiwen Xia, Shaoqian Zhang, Hongxi Yang, Yingxue Zou","doi":"10.1002/bcp.70055","DOIUrl":"https://doi.org/10.1002/bcp.70055","url":null,"abstract":"<p><strong>Background: </strong>Early-life and prolonged exposure to antibiotics has been associated with various health issues. This study aimed to explore the relationship between early-life antibiotic exposure and different health outcomes from the perspective of epidemiology.</p><p><strong>Methods: </strong>Using electronic hospital records, questionnaire data and genotype information from the UK Biobank, this study analysed 158 391 individuals with early-life and prolonged antibiotics exposure to investigate its association with 78 common diseases. After adjusting for covariates, we conducted an observational study to explore the relationships between antibiotic use and various diseases. Subsequently, a genome-wide association analysis was performed on early-life and prolonged antibiotics use, and eight Mendelian randomization methods were applied with instrumental variables to account for confounding factors and explore potential causal relationships.</p><p><strong>Results: </strong>In our observational study involving 78 common diseases, our findings revealed significant associations between exposure to antibiotics during early life and 42 diseases, after correcting the false discovery rate. Among these, 8 diseases demonstrated causal evidence. These diseases include type-2 diabetes (odds ratio [OR] with 95% confidence interval [95% CI] = 1.27 [1.18, 1.36], P = 4.8 × 10^-11), depression (OR = 1.77 [1.67, 1.89], P = 2.2 × 10^-72), inflammatory bowel disease (OR = 1.28 [1.14, 1.45], P = 6.2 × 10^-5), polymyalgia rheumatica (OR = 1.28 [1.07, 1.53], P = 6.4 × 10^-3), giant cell arteritis (OR = 1.55 [1.12, 2.14], P = 7.5 × 10^-3), sciatica (OR = 1.54 [1.35, 1.76], P = 8.3 × 10^-11), cystitis (OR = 1.51 [1.31, 1.74], P = 8.1 × 10^-9) and bronchiectasis (OR = 2.70 [2.37, 3.06], P = 9.7 × 10^-52).</p><p><strong>Conclusion: </strong>This study revealed the enduring and detrimental effects of prolonged antibiotic usage during early life, which can potentially result in the development of diseases across multiple bodily systems.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An oral robotic pill reliably and safely delivers teriparatide with high bioavailability in healthy volunteers: A phase 1 study.","authors":"Joshua T Myers, Alyson Yamaguchi, April Toledo Vo, Anvesh Dasari, Archana Battiwala, Nidhi Patel, Leonard C Fung, Ofer M Gonen, Mir Imran, Jacques Van Dam, Mir A Hashim, Arvinder K Dhalla, John P Bilezikian","doi":"10.1002/bcp.70064","DOIUrl":"https://doi.org/10.1002/bcp.70064","url":null,"abstract":"<p><strong>Aims: </strong>The incidence of osteoporosis is projected to exceed 70 million people over the age of 65 years by 2030. Osteoanabolic agents, such as teriparatide and abaloparatide, are not only effective in reducing fracture incidence but also improve skeletal microstructure-an important need not met by antiresorptive agents. However, anabolic agents must be administered by daily subcutaneous injections which can be a challenge in older women. To address this need, we have developed an oral robotic pill (RP) designed to deliver biotherapeutics safely and painlessly.</p><p><strong>Methods: </strong>This report describes the results of a 2-part Phase 1 study conducted to evaluate the safety, tolerability and pharmacokinetics of single (Part 1) and repeat doses (Part 2) of teriparatide delivered via the RP (RT-102) in healthy and postmenopausal women.</p><p><strong>Results: </strong>Teriparatide, administered by the RP, was measurable in 26/29 and 63/69 of participants in Part 1 and Part 2, respectively. RT-102 at the 20-μg dose yielded a lower maximum observed serum concentration (98 ± 10 vs. 128 ± 20 pg mL^-1), delayed time to reach maximum observed serum concentration (68 ± 15 vs. 13 ± 2 min) and higher area under the curve to infinity (342 ± 44 vs. 126 ± 29 h pg mL^-1) resulting in a 3-fold higher bioavailability than subcutaneous injection. RT-102 was well tolerated with only 5 mild to moderate adverse events (AEs) related to the RP that resolved without intervention and no serious AEs. Drug-related AEs were similar in severity and frequency between RT-102 and subcutaneous teriparatide.</p><p><strong>Conclusion: </strong>These data demonstrate that RT-102 can safely and reliably deliver therapeutic levels of teriparatide.</p><p><strong>Clinicaltrials: </strong>GOV: NCT#05164614.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EudraVigilance insights: Suspected adverse drug reactions in infants through breastfeeding.","authors":"Ida M Heerfordt, Ditte Resendal Gotfredsen, Henrik Horwitz, Anette Kirstine Stark, Jon Trærup Andersen, Christina Gade, Ulrik Lausten-Thomsen, Rasmus Huan Olsen","doi":"10.1002/bcp.70063","DOIUrl":"https://doi.org/10.1002/bcp.70063","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to describe suspected adverse drug reactions (ADRs) in infants resulting from medications transmitted through mothers' milk, as reported to the European ADR database, EudraVigilance. The research sought to understand the frequency, seriousness and nature of these ADRs to assess potential risks associated with maternal medication use during breastfeeding.</p><p><strong>Methods: </strong>Data from EudraVigilance were analysed. The study included all reported ADRs suspected to be related to medications transmitted through mothers' milk from 1 January 2013 to 1 July 2023. The data were categorized by reporting time, infant age and sex, seriousness and type of ADR, and the medications involved.</p><p><strong>Results: </strong>A total of 922 suspected ADRs were reported in breastfed infants. Serious ADRs accounted for 133 cases (14%), with 15 reported fatalities, primarily associated with methadone (n = 11) and diamorphine (n = 3). COVID-19 vaccines were linked to half of the suspected ADR reports (n = 479, 52%), while serious ADRs were mainly associated with nervous system drugs (n = 73, 43%), particularly anticonvulsants and opioids. Most cases (n = 511, 55%) occurred in infants aged between 1 month and 1 year.</p><p><strong>Conclusions: </strong>The reporting of 922 ADRs in breastfed infants over a decade, compared to the estimated millions of infants exposed to medications via mothers' milk annually in Europe, suggests a very low reporting rate of suspected ADRs. This finding emphasizes the significant challenges in postmarketing surveillance and suggests that underreporting remains a critical concern in pharmacovigilance.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Space travel-associated motion sickness and its treatment.","authors":"Jay C Buckey, Mimi Lan, Lionel D Lewis","doi":"10.1002/bcp.70056","DOIUrl":"https://doi.org/10.1002/bcp.70056","url":null,"abstract":"<p><p>On Earth, motion sickness is often just a nuisance that can spoil a car ride, fishing trip, or visit to an amusement park. In space, however, motion sickness can be hazardous. Vomiting due to motion sickness while in a space suit could lead to aspiration, poor visibility and damage to space suit systems. The effects motion sickness has on alertness and mental performance are undesirable when critical operations are underway. Although motion sickness has been an issue for space travellers since the beginning of human space exploration, the range of medications and routes of administration have not changed appreciably since the early days of spaceflight, which spans more than 40 years. This review presents the main therapeutics available for space-induced motion sickness, the routes of administration available, and the challenges for administering them in space while minimizing major side effects.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the acute effects of single-dose TPN171 on semen quality in healthy Chinese male volunteers.","authors":"Yuzhuo Yang, Zhe Zhang, Lei Li, Zhicheng Jiang, Jiaxiang Juan, Huaqing Duan, Zhen Wang, Hui Jiang","doi":"10.1002/bcp.70049","DOIUrl":"https://doi.org/10.1002/bcp.70049","url":null,"abstract":"<p><strong>Aims: </strong>TPN171 is a novel phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction. This study aimed to assess the immediate impact of a single dose of TPN171 (10 mg) on semen quality in healthy male Chinese volunteers. Additionally, the study investigated the exposure of TPN171 in seminal plasma and observed the safety of TPN171 in the participants.</p><p><strong>Methods: </strong>Eighteen healthy male volunteers were enrolled in this double-blind, randomized, placebo-controlled, 2-period, 2-sequence, crossover study. Semen samples were collected to compare semen parameters between the TPN171 and placebo groups. The concentrations of TPN171 were measured in seminal plasma and blood plasma to calculate the ratio of TPN171 concentration in seminal plasma to that in blood plasma, along with the exposure level and percentage of TPN171 in the seminal plasma.</p><p><strong>Results: </strong>The administration of a single 10-mg dose of TPN171 did not result in statistically significant effects on sperm motility, count, density, morphology, viscosity or volume in healthy male Chinese volunteers. The ratio of TPN171 concentration in seminal plasma to that in blood plasma was 0.72, with the amount of TPN171 in the seminal plasma measured at 78.5 ng. The percentage of exposure to the administered dose (10 mg) was 0.00085%. No adverse events were reported in the TPN171 group.</p><p><strong>Conclusion: </strong>The findings indicate that a single oral dose of 10 mg TPN171 did not induce acute effects on semen quality in healthy male Chinese volunteers. The exposure of seminal plasma to TPN171 was <0.001% of the administered dose.</p><p><strong>Clinical trial registration number: </strong>NCT05585931.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning approach for dosage individualization of azithromycin in children with community-acquired pneumonia.","authors":"Bo-Hao Tang, Shu-Meng Fu, Li-Yuan Tian, Xin-Fang Zhang, Bu-Fan Yao, Wei Zhang, Yue-E Wu, Yue Zhou, Ya-Kun Wang, Guo-Xiang Hao, John van den Anker, Yi Zheng, Wei Zhao","doi":"10.1002/bcp.70050","DOIUrl":"https://doi.org/10.1002/bcp.70050","url":null,"abstract":"<p><strong>Aims: </strong>The uncertainty about the efficacy and safety of currently used azithromycin dosing regimens in children warrants individualized therapy. The area under the plasma concentration-time curve over 24 h (AUC_0-24) of azithromycin correlates best with its effectiveness. The aim of this study was to evaluate the ability of machine learning (ML) to predict the AUC_0-24 of azithromycin in children with community-acquired pneumonia.</p><p><strong>Methods: </strong>Various ML algorithms were used to build ML models based on simulated pharmacokinetic profiles from a published population pharmacokinetic model. A priori-ML model predicted AUC_0-24 using patients' characteristics and after the trough concentration (C₀) became available, a posteriori-ML model was built for improved prediction. Statistical methods and pharmacodynamic (PD) evaluation methods were used to evaluate the ML model's predictive accuracy in a real-world study. ML-optimized doses were evaluated by calculating the probability of PD target attainment in virtual trials compared with guideline-recommended doses.</p><p><strong>Results: </strong>The AUC_0-24 can be predicted by priori-ML model using the CatBoost algorithm with dosing regimen and two covariates as predictors (weight, alanine aminotransferase) before initial administration. A posteriori-ML model using CatBoost algorithm was built with adding C₀ as a predictor. In real-world validation, the mean absolute prediction error of the priori-ML and posteriori-ML models was less than 30%. The accuracy (determining whether the PD target is met) of the priori-ML model was 76.3%, whereas that of the posteriori-ML model increased to 90.4%.</p><p><strong>Conclusions: </strong>ML models were established to predict the AUC_0-24 of azithromycin successfully and could be used for individual dose adjustment in children before treatment and after obtaining C₀.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}